This project focuses on partial or total synthesis of biologically important peptides which 1) in corporate unique structural features as functionally important probes or for defined linkages to proteins, 2) represent portions of the sequence of proteins and are useful for immunological investigations, 3) display agonism or antagonism through substitutions of amino acid residues or changes in secondary structures. A. Specific toxicity has been programmed into ovine corticotropin- (oCRF) and human growth hormone (hGHRH) releasing hormones by way of derivatization with an active ester of 10B enriched 1-(2- carboxymethyl)-1,2-dicarba-closododecarborane after the standard Merrifield solid phase peptide synthesis. In order to prevent perturbation of biological activity, carboranyl acetylation was directed to the alpha-amino terminus of oCRF or the introduced epsilon-amino group of Lys at residue 41 for GHRH. The derivatives are fully active for their respective hormone releasing activities, and the labelled oCRF was able to suppress the ACTH release system upon irradiation with slow neutron gas without affecting the releases ofGH, LH and prolactin in a pituitary cell culture system. Neutron radiation experiments with the labelled hGHRH are now in progress. B. Substitutions of Ala at Gly13, Gly18 within the magainin 2 amide sequence in order to enhance the potential of an amphiphilic alpha-helical conformation as revealed by the circular dichroism resulted in one to two order of magnitude increase of antimicrobial activity over magainin 2 in a wide variety of bacteria. The importance of a free amino-terminus for the full activity was also established. C. Synthesis of a 27 residue peptide deduced from mouse proto- oncogene c-fos with Tyr as the amino-terminus was accomplished- The peptide was conjugated to bovine thyroglobulin by diazotized benzidine through phenolic function of Tyr.